LncRNAs exhibit subtype-specific expression, survival associations, and cancer-promoting effects in breast cancer.

Long non-coding RNAs (lncRNAs) play important roles in cancer progression, influencing processes such as invasion, metastasis, and drug resistance. Their reported cell type-dependent expression patterns suggest the potential for specialized functions in specific contexts. In breast cancer, lncRNA expression has been associated with different subtypes, highlighting their relevance in disease heterogeneity.

ALDH1A3 promotes invasion and metastasis in triple-negative breast cancer by regulating the plasminogen activation pathway.

Aldehyde dehydrogenase 1A3 (ALDH1A3) is a cancer stem cell marker that promotes metastasis. Triple-negative breast cancer (TNBC) progression has been linked to ALDH1A3-induced gene expression changes. To investigate the mechanism of ALDH1A3-mediated breast cancer metastasis, we assessed the effect of ALDH1A3 on the expression of proteases and the regulators of proteases that degrade the extracellular matrix, a process that is essential for invasion and metastasis.

The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond.

Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism.

Isolation of cancer stem cells from cultured breast cancer cells and xenografted breast tumors based on aldehyde dehydrogenase activity.

The heterogeneity of breast tumors is a major factor in the development, progression, and therapeutic response of breast cancer. In terms of therapy resistance, a subset of tumor cells commonly referred to as cancer stem cells (CSCs) or tumor initiating cells (TICs) have a prominent role. These cells have inherent increased tumorigenicity, self-renewal and differentiation capacity, and mechanisms for chemotherapy and radiation resistance.

Datasets exploring putative lncRNA-miRNA-mRNA axes in breast cancer cell lines.

Long non-coding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) interactions regulate oncogenesis and tumour suppression in breast cancer. Oncogenic lncRNA/miRNA/mRNA axes may offer novel therapeutic targets; therefore, identifying such axes is a clinically relevant undertaking. To explore miRNAs regulated by oncogenic lncRNAs, we queried the NCBI Gene Expression Omnibus (GEO) database to find datasets that profiled gene expression changes upon lncRNA knockdown in breast cancer.

LncRNA Promotes Proliferation and Migration, Is Associated with Cancer Stem Cells, and Alters the miRNA Landscape in Triple-Negative Breast Cancer.

Triple-negative breast cancers (TNBCs) are aggressive, lack targeted therapies and are enriched in cancer stem cells (CSCs). Novel therapies which target CSCs within these tumors would likely lead to improved outcomes for TNBC patients. Long non-coding RNAs (lncRNAs) are potential therapeutic targets for TNBC and CSCs.

LncRNA-miRNA axes in breast cancer: Novel points of interaction for strategic attack.

Therapeutic effectiveness in breast cancer can be limited by the underlying mechanisms of pathogenesis, including epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and drug resistance. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are master regulators of gene expression and are functionally important mediators in these mechanisms of pathogenesis. Intricate crosstalks between these non-coding RNAs form complex regulatory networks of post-transcriptional gene regulation.

Novel strategies to target chemoresistant triple-negative breast cancer.

Previous studies from our group and others have shown that current drug treatment(s) strategies eliminate bulk of tumor cells (non-CSCs) but it had a minimal effect on cancer stem cells (CSCs) leading to resistance and tumor recurrence. We studied the effects of CFM-4.16 (CARP-1 functional mimetic) and/or cisplatin on four Triple-negative breast cancer (TNBC) MDA-MB-468, MDA-MB-231, CRL-2335 and BR-1126, two cisplatin resistant CisR/MDA-231 and CisR/MDA-468 and cancer stem cells (CSCs) from resistant cell lines.

Antagonizing binding of cell cycle and apoptosis regulatory protein 1 (CARP-1) to the NEMO/IKKγ protein enhances the anticancer effect of chemotherapy.

NF-κB is a pro-inflammatory transcription factor that critically regulates immune responses and other distinct cellular pathways. However, many NF-κB-mediated pathways for cell survival and apoptosis signaling in cancer remain to be elucidated. Cell cycle and apoptosis regulatory protein 1 (CARP-1 or CCAR1) is a perinuclear phosphoprotein that regulates signaling induced by anticancer chemotherapy and growth factors.

A H2AX⁻CARP-1 Interaction Regulates Apoptosis Signaling Following DNA Damage.

Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage.

A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers.

Non-small cell lung cancers (NSCLC) account for 85% of all lung cancers, and the epidermal growth factor receptor (EGFR) is highly expressed or activated in many NSCLC that permit use of EGFR tyrosine kinase inhibitors (TKIs) as frontline therapies. Resistance to EGFR TKIs eventually develops that necessitates development of improved and effective therapeutics. CARP-1/CCAR1 is an effector of apoptosis by Doxorubicin, Etoposide, or Gefitinib, while CARP-1 functional mimetic (CFM) compounds bind with CARP-1, and stimulate CARP-1 expression and apoptosis.

Using a Prediction Model to Manage Cyber Security Threats.

Cyber-attacks are an important issue faced by all organizations. Securing information systems is critical. Organizations should be able to understand the ecosystem and predict attacks.